[Show abstract][Hide abstract] ABSTRACT: Clomiphene citrate (CC) is the first line drug for ovulation induction but because of its peripheral antiestrogenic effect, letrozole was introduced as the 2nd line drug. It lacks the peripheral antiestrogenic effect and is associated with similar or even higher pregnancy rates. Since letrozole is a drug for breast cancer, its use for the purpose of ovulation induction became controversial in the light of studies indicating an increased incidence of congenital malformations.
PLoS ONE 01/2014; 9(10):e108219. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Letrozole, a selective aromatase inhibitor, reduces the total dose of gonadotrophin required for inducing follicular maturation. We evaluated if incorporation of letrozole could be an effective alternative for low-cost in vitro fertilization (IVF) protocol particularly in intracytoplasmic sperm injection (ICSI) cycles where male factor infertility is the sole indication for IVF.
It is a randomized controlled single-blind trial. 94 women with history of severe male factor infertility were selected. 42 women (study group) received letrozole, 5 mg daily from day 3-7 and recombinant FSH (rFSH) 75IU/day from day 5 continuously till hCG injection. 52 women (control group) underwent continuous stimulation by rFSH (150-225IU/day) from day 2. GnRH-antagonist (Inj. Orgalutran 0.25 ml sub-cutaneous) was started at maximum follicle size of 14 in both groups. Ovulation was triggered by 10,000IU of hCG followed by IVF-ET. Main outcome measures were total dose of rFSH (IU/cycle), terminal E2 (pg/ml), number of mature follicles, number of oocyte retrieved, transferable embryo, endometrial thickness, pregnancy rate and mean expenditure. Statistical analysis is done by using SPSS11.
As compared to control group (1756 ± 75IU), the study group i.e., Let-rFSH received (625 ± 98IU) significantly lower (P = 0.0001) total dose of rFSH. Terminal E2 was significantly lower (P = 0.0001) in study group than control (830 ± 36 vs. 1076 ± 41 pg/ml) with significant increment in endometrial thickness (P = 0.0008) in study group, (9.1 ± 0.32 vs. 8.7 ± 0.69) which maintained an improved pregnancy rate though nonsignificant. The risk of hyperstimulation had significantly (P = 0.01) reduced in study group than control (0 vs. 7).Treatment outcome in all other aspects including pregnancy rate were statistically comparable. Per cycle mean expenditure was reduced by 34% in study group than control.
Adjunctive use of letrozole may be an effective mean of low-cost IVF therapy.
Journal of human reproductive sciences. 05/2012; 5(2):170-4.
[Show abstract][Hide abstract] ABSTRACT: The ideal method for sperm selection during Intracytoplasmic sperm injection (ICSI) is still ill-defined. Identification of a viable spermatozoon amongst immotile spermatozoa for ICSI often becomes difficult. Ninety-six ICSI cycles were selected and divided into Group A (azoospermic, n = 58) and Group B (complete asthenozoospermic, n = 38). Oocytes having birefringent meiotic spindle and zona pellucida thickness <20 μm were selected for ICSI. Groups A and B were further divided into A1, A2 and B1, B2, respectively, based on the type of ICSI performed. In Group A1, a motile spermatozoon with normal morphology was injected into a metaphase-II (M-II) oocyte. In Group B1, spermatozoon showing coiling of tail following modified hypo-osmotic swelling test was injected into M-II oocytes. In Groups A2 and B2, ICSI was performed by injecting a spermatozoan with birefringent head. Pronuclear morphology, fertilisation rate, embryo grading and pregnancy rate were assessed. ICSI outcome measures were better in Group A2 than in Group A1 but were statistically insignificant. However, significantly higher percentage of Z1 and Z2 zygotes, Grade I and Grade II embryos and pregnancy rate were observed in Group B2 as compared to Group B1. Selection of birefringent spermatozoa shows promising results in asthenozoospermic men and men undergoing testicular sperm aspiration or extraction before ICSI.
[Show abstract][Hide abstract] ABSTRACT: A large prospective clinical trial was conducted to compare the efficacy of single dose uFSH and clomiphene citrate combination with clomiphene citrate alone for ovulation induction to improve the pregnancy rate.
The study was a randomized, prospective clinical trial. Totally, 1527 infertile women (4381 cycles) with polycystic ovarian syndrome (PCOS) (n=911/2573 cycles) and unexplained infertility (n=616/1808 cycles) were randomized into two groups. Group A received single dose of uFSH on D(3) of menstrual cycle along with clomiphene. Group B received clomiphene only for ovulation induction. We compared the pregnancy rate and miscarriage rate between two groups.
Group A had a pregnancy rate of 17% compared to 8.3% of Group B which was significantly higher (P=0.0001). The miscarriage rate was 11% in Group A and 10% in Group B which was not significant (P=0.99). Pregnancy rates in PCOS women were 22% in Group A and 9.3% in Group B which shows significantly higher pregnancy rate (P=0.0001) in anovulatory infertility. But in unexplained infertility, there was no significant difference in pregnancy rate between Group A (11%) and Group B(6.3%). Miscarriage rates were 8.8% and 9.5% in Group A and Group B, respectively, in PCOS women and 14% and 13% in women with unexplained infertility.
Addition of single dose of uFSH improves pregnancy outcome particularly in anovulatory infertility (WHO II). Correction of unexplained infertility may need more than simple correction of possible subtle ovulatory effect.
Journal of human reproductive sciences. 05/2010; 3(2):80-4.
[Show abstract][Hide abstract] ABSTRACT: The effect of follicular fluid (FF) oxidative stress (OS) on meiotic spindle (MS) formation in oocytes and subsequent outcome in women with polycystic ovarian syndrome (PCOS) are evaluated in this study.
326 oocytes from 35 PCOS women (group A) and 208 oocytes from 32 women with tubal infertility (group B) were visualized for MS using PolScope. FF was analyzed for OS markers including reactive oxygen species (ROS), lipid peroxidation and total antioxidant capacity (TAC). Group A was further classified into groups A1 and A2, and group B into groups B1 and B2 depending upon the presence or absence of MS, respectively.
MS formation was absent in a significantly higher number of oocytes in group A compared to group B (p <or= 0.05). OS markers were significantly higher in group A compared to group B (p <or= 0.05). Fertilization rate, number of good quality embryos and clinical pregnancy rates were higher in group B compared to group A, though not statistically significant. FF ROS was significantly higher and TAC significantly lower in groups A2 and B2 compared to groups A1 and B1 (p < 0.001).
The presence of MS and oocyte maturation in PCOS women showed a positive correlation with low levels of OS.
Gynecologic and Obstetric Investigation 01/2010; 69(3):197-202. · 1.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The impact of oxidative stress in female reproduction is not clear. Contradictory reports on the effect of various oxidative stress markers on follicular fluid, oocytes and embryo quality and fertilization potential exist. The objectives of this study were to examine reactive oxygen species (ROS) levels in follicular fluid of women undergoing IVF and to relate these levels to embryo formation and quality.
A total of 208 follicular fluid samples were obtained from 78 women undergoing controlled ovarian stimulation and analysed for ROS and lipid peroxidation (LPO). These samples were divided into groups I and II which represented follicular fluid containing grade III and grade II oocytes, respectively. These groups were further subdivided into groups IA, IB, IIA and IIB according to embryo quality. Subgroups IA and IIA consisted of follicular fluid samples corresponding to grade I/II embryo formation. Subgroups IB and IIB represented fertilization failure/pro-nucleolus (PN) arrest/grade III embryos. No significant correlation was observed in ROS levels on comparing groups I and II (P > 0.05). However, ROS levels were observed to be significantly different on comparing groups IA and IB (P < or = 0.01) and groups IIA and IIB (P < or = 0.05). LPO levels further supported our results.
ROS levels in follicular fluid appear to play a significant role in embryo formation and quality.
Human Reproduction 09/2006; 21(9):2403-7. · 4.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Use of letrozole, a selective inhibitor of aromatase, reduces the gonadotrophin dose required to induce follicular maturation. We evaluated whether incorporation of letrozole could be an effective low-cost IVF protocol for poor responders.
A randomized, controlled, single-blind trial was conducted in the Assisted Reproduction Unit, Institute of Reproductive Medicine, Kolkata, India. Thirty-eight women with a history of poor ovarian response to gonadotrophins were recruited. Thirteen women (Let-FSH group) received letrozole 2.5 mg daily from day 3-7, and recombinant FSH (rFSH) 75 IU/day on days 3 and 8; and 25 women (GnRH-ag-FSH group) underwent long GnRH agonist protocol and stimulated with rFSH (300-450 IU/day). Ovulation was triggered by 10,000 IU of HCG followed by IVF-embryo transfer. The main outcome measures were total dose of rFSH (IU/cycle), terminal estradiol (E2) (pg/ml), numbers of follicles, oocytes retrieved and transferable embryo, endometrial thickness (mm), and pregnancy rate.
Compared with the GnRH-ag-FSH group (2865 +/- 228 IU), the Let-FSH group (150 +/- 0 IU) received a significantly (P < 0.001) lower total dose of FSH. Except for terminal E2, which was significantly higher (P < 0.001) in the GnRH-ag-FSH group (380 +/- 46 pg/ml) than the Let-FSH group (227 +/- 45 pg/ml), the treatment outcomes in all other respects, including pregnancy rate, were statistically comparable.
Adjunctive use of letrozole may form an effective means of low-cost IVF protocol in poorly responding women.
Human Reproduction 09/2004; 19(9):2031-5. · 4.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The pathophysiological mechanisms underlying premature ovarian failure (POF) are largely unknown. Our objective was to develop a working animal model to explore the pathogenesis of POF. Since galactosaemic women eventually develop POF, we evaluated the potential of experimental galactose toxicity as the proposed model.
Pregnant rats were fed pellets supplemented with or without 35% galactose from day 3 of conception continuing through weaning of the litters. Female offspring were evaluated for serum levels of galactose and galactose-1-phosphate, growth rate, onset of puberty, reproductive cyclicity, ovarian complement of follicles, hypothalamo-pituitary-ovarian function and follicular response to gonadotrophins.
Galactose toxicity delayed the onset of puberty and developed a state of hypergonadotrophic hypoestrogenism. The characteristic low FSH levels at weaning followed by pubertal spurts of gonadotrophins and estradiol (E(2)) secretion of the controls was replaced by a sustained high level of FSH and a low level of E(2) under galactose toxicity. The ovary developed with apparently normal or deficient complement of follicles. Ovarian response to exogenous gonadotrophin stimulation was blunted, but the response improved significantly when the stimulation was preceded by pituitary desensitization.
Experimental galactose toxicity may serve as a model for exploring some of the basic tenets of POF.
Human Reproduction 11/2003; 18(10):2031-8. · 4.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In rats, prenatal exposure to high concentrations of galactose may contribute to a condition that is equivalent to the premature ovarian failure (POF) component of human galactosaemia. We investigated if development of POF under experimental galactosaemia-like conditions was attributed to impaired germ cell migration.
Pregnant rats were fed pellets supplemented with, or without, 35% galactose from day 3 of conception continuing through parturition. Between days 12-15, embryos from one uterine horn were dissected out. Primordial germ cells (PGC) were histochemically localized and counted on the basis of binding of Dolichos biflorus agglutinin, a lectin specific for terminal N-acetylgalactosamine (GalNAc), to the surface glycoconjugate of the germ cells. The embryos from the other uterine horn were maintained until parturition. Liver activity of uridine diphosphate galactose 4-epimerase, the enzyme involved at multiple steps in the process of synthesis of GalNAc, was assayed in 1-2 day old female pups.
The numbers of PGC at the day-specific sites on all days of examination were significantly lower (P </= 0.0003), and liver epimerase activity was significantly (P = 0.000001) reduced in the galactose-exposed group.
Impaired germ cell migration leading to the development of gonads with deficient initial pools of germ cells may form the causal link between galactosaemia and POF.
Human Reproduction 02/2003; 18(2):276-82. · 4.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Our purpose was to evaluate the IVF-ET outcome in patients who did not achieve timely pituitary-ovarian suppression following "long"-protocol GnRH agonist (GnRH-a) administration.
A retrospective analysis was done on 96 IVF treatment cycles characterized by a delayed response (DR) to long-protocol GnRH-a treatment. The study included those patients who either achieved ovarian suppression (E2 < or = 110 pM) despite an elevated LH level (group DR-A) or had pituitary desensitization (LH < or = 1.5 IU/L) without ovarian suppression (group DR-B) on day 12 of GnRH-a treatment but needed an extended course of GnRH-a treatment to achieve complete suppression. These patients had gonadotropin stimulation either from day 12, despite an elevated level of LH (subgroup DR-A1; n = 13) or elevated E2 levels (subgroup DR-B1; n = 9), or after achieving a complete hypogonadotropic-hypopgonadal state following an extended course of GnRH-a treatment [subgroups DR-A2 (n = 46) and DR-B2 (n = 28)]. The outcome was compared with that of 88 cycles of normal responders (group NR) who had pituitary-ovarian suppression by day 12 day GnRH-a administration.
Ovarian response and pregnancy rates in subgroups DR-A1 and DR-A2 were statistically not different and comparable to those in the NR group. In subgroups DR-B1 and DR-B2, E2 response and rates of oocyte retrieval and pregnancy were significantly lower than those in the other groups, but fertilization and cleavage rates were similar. The requirement of gonadotropin for ovarian stimulation was comparatively higher in subgroup DR-A2 and both DR-B subgroups.
There was no treatment cancellation in group NR and both DR-A subgroups, but 22% of the cycles in DR-B1 and 14% of the cycles in DR-B2 were canceled due to poor ovarian response. It therefore appears that during long-protocol pituitary desensitization, the post-GnRH-a level of serum E2, rather than LH, better predicts IVF-ET outcome.
Journal of Assisted Reproduction and Genetics 06/1996; 13(5):374-80. · 1.82 Impact Factor